Department of Clinical Sciences Lund, Anaesthesiology and Intensive Care, Skane University Hospital, Lund University, Lund, Sweden.
Department of Clinical Sciences Lund, Infection Medicine, Skane University Hospital, Lund University, Lund, Sweden.
Acta Anaesthesiol Scand. 2020 Aug;64(7):982-991. doi: 10.1111/aas.13598. Epub 2020 Apr 21.
The Gram-negative bacterium Escherichia coli, commonly involved in severe sepsis and septic shock, shed endotoxin that upon detection by the host triggers an inflammatory cascade. Efficiency of albumin solutions to restore hypovolemia during sepsis has been debated. To aid identification of subgroups of sepsis patients that may respond positively or negatively to treatment with albumin we investigated if preparations of albumin for medical use could affect endotoxin-induced inflammatory response.
Isolated human omental arteries obtained during surgery were incubated with endotoxin in the presence or absence of albumin solution. Isolated human monocytes were incubated with endotoxin in the presence or absence of five different commercially available albumin solutions. Vascular contractile response to noradrenaline and release of interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α were measured.
Incubation with albumin together with endotoxin decreased median maximum contraction and increased release of IL-6 and IL-8 from the arteries compared to incubation with endotoxin alone. All albumin solutions except one significantly increased endotoxin-induced TNF-α release from monocytes. IL-6 and IL-10 were also increased and no concentration dependency of TNF-α release was observed above 2 mg mL . Incubation with albumin alone did not affect contraction or release of cytokines while no potentially endotoxin-enhancing contaminant could be identified.
We have shown that albumin solution in combination with endotoxin cause vasoplegia in human omental arteries, paralleled by an inflammatory response. This finding could explain the variable efficiency of albumin solutions for sepsis treatment.
革兰氏阴性菌大肠杆菌通常与严重败血症和感染性休克有关，其脱落的内毒素被宿主检测到时会引发炎症级联反应。在败血症期间，白蛋白溶液恢复血容量的效率一直存在争议。为了帮助确定可能对白蛋白治疗产生积极或消极反应的败血症患者亚组，我们研究了用于医疗的白蛋白制剂是否会影响内毒素诱导的炎症反应。
在手术中获得的分离人网膜动脉在存在或不存在白蛋白溶液的情况下与内毒素孵育。分离的人单核细胞在存在或不存在五种不同市售白蛋白溶液的情况下与内毒素孵育。测量去甲肾上腺素引起的血管收缩反应和白细胞介素 (IL)-1β、IL-6、IL-8、IL-10 和肿瘤坏死因子 (TNF)-α 的释放。
与单独孵育内毒素相比，与内毒素一起孵育白蛋白可降低动脉的最大收缩中位数，并增加 IL-6 和 IL-8 的释放。除一种外，所有白蛋白溶液均显著增加单核细胞中内毒素诱导的 TNF-α释放。IL-6 和 IL-10 也增加了，并且在 2mg/mL 以上未观察到 TNF-α释放的浓度依赖性。单独孵育白蛋白不会影响收缩或细胞因子的释放，同时也没有发现潜在的增强内毒素的污染物。
我们已经表明，白蛋白溶液与内毒素结合会导致人网膜动脉血管扩张，同时伴有炎症反应。这一发现可以解释白蛋白溶液治疗败血症的效率差异。
